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Brain Somatic Mutations in MTOR Disrupt Neuronal Ciliogenesis, Leading to Focal Cortical Dyslamination

DC Field Value Language
dc.contributor.author강훈철-
dc.contributor.author김동석-
dc.contributor.author김세훈-
dc.contributor.author김형범-
dc.date.accessioned2018-11-16T16:52:43Z-
dc.date.available2018-11-16T16:52:43Z-
dc.date.issued2018-
dc.identifier.issn0896-6273-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/165425-
dc.description.abstractFocal malformations of cortical development (FMCDs), including focal cortical dysplasia (FCD) and hemimegalencephaly (HME), are major etiologies of pediatric intractable epilepsies exhibiting cortical dyslamination. Brain somatic mutations in MTOR have recently been identified as a major genetic cause of FMCDs. However, the molecular mechanism by which these mutations lead to cortical dyslamination remains poorly understood. Here, using patient tissue, genome-edited cells, and mouse models with brain somatic mutations in MTOR, we discovered that disruption of neuronal ciliogenesis by the mutations underlies cortical dyslamination in FMCDs. We found that abnormal accumulation of OFD1 at centriolar satellites due to perturbed autophagy was responsible for the defective neuronal ciliogenesis. Additionally, we found that disrupted neuronal ciliogenesis accounted for cortical dyslamination in FMCDs by compromising Wnt signals essential for neuronal polarization. Altogether, this study describes a molecular mechanism by which brain somatic mutations in MTOR contribute to the pathogenesis of cortical dyslamination in FMCDs.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherCell Press-
dc.relation.isPartOfNEURON-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleBrain Somatic Mutations in MTOR Disrupt Neuronal Ciliogenesis, Leading to Focal Cortical Dyslamination-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pediatrics (소아청소년과학교실)-
dc.contributor.googleauthorSang Min Park-
dc.contributor.googleauthorJae Seok Lim-
dc.contributor.googleauthorSuresh Ramakrishina-
dc.contributor.googleauthorSe Hoon Kim-
dc.contributor.googleauthorWoo Kyeong Kim-
dc.contributor.googleauthorJunehawk Lee-
dc.contributor.googleauthorHoon-Chul Kang-
dc.contributor.googleauthorJeremy F. Reiter-
dc.contributor.googleauthorDong Seok Kim-
dc.contributor.googleauthorHyongbum (Henry) Kim-
dc.contributor.googleauthorJeong Ho Lee-
dc.identifier.doi10.1016/j.neuron.2018.05.039-
dc.contributor.localIdA00102-
dc.contributor.localIdA00402-
dc.contributor.localIdA00610-
dc.contributor.localIdA01148-
dc.relation.journalcodeJ02345-
dc.identifier.eissn1097-4199-
dc.identifier.pmid29937275-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0896627318304379-
dc.subject.keywordMTOR-
dc.subject.keywordbrain somatic mutation-
dc.subject.keywordfocal malformations of cortical development-
dc.subject.keywordprimary cilia-
dc.contributor.alternativeNameKang, Hoon Chul-
dc.contributor.alternativeNameKim, Dong Seok-
dc.contributor.alternativeNameKim, Se Hoon-
dc.contributor.alternativeNameKim, Hyongbum-
dc.contributor.affiliatedAuthor강훈철-
dc.contributor.affiliatedAuthor김동석-
dc.contributor.affiliatedAuthor김세훈-
dc.contributor.affiliatedAuthor김형범-
dc.citation.volume99-
dc.citation.number1-
dc.citation.startPage83-
dc.citation.endPage97-
dc.identifier.bibliographicCitationNEURON, Vol.99(1) : 83-97, 2018-
dc.identifier.rimsid58890-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers

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